Major neuropsychiatric disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia and depression are associated with and in some cases caused by chemical imbalances in the brain. The purpose of this research is to develop probes that can be used to assess these chemical imbalances so as to better understand these disorders and hopefully to improve their treatments. A major goal of the Molecular Imaging Branch is to develop new radiotracers and new imaging paradigms to study abnormal protein targets in patients with neuropsychiatric disorders. The purpose of this research is to evaluate in vivo the pharmacokinetics, sensitivity and reproducibility of brain imaging measurements of radiolabeled probes for use in positron emission tomography (PET). Animals will be used to evaluate new tracers and new methods (e.g., combined with a pharmacological challenge) prior to their use in human subjects. Testing of these tracers in animals prior to their extension to humans is essential to ensure the validity of the measurement and the safety of the procedures. During the prior year (October 2004 - September 2005), our projects have included: 1) Development of a probe for Alzheimer's disease. Significant progress has been made to develop a probe that could be used to diagnose and monitor Alzheimer's disease by labeling a protein that accumulates in the brains of patients with this disorder. 2) Evaluation of a probe for intracellular signals. Most of the available probes label targets (or receptors) located on the outside of the cell. We are now examining a probe for an intracellular target (phosphodiesterase) that is believed to be involved in the therapeutic actions of antidepressant treatments. 3) Evaluation for probe in Parkinson's disease. In collaboration with NINDS, we imaged a target (the dopamine transporter) that was successfully used to monitor brain cell transplantation treatment of rat with an animal model of Parkinson's disease. 4) Probe for the cannibinoid receptor, which mediates the effects of marijuana. 5) Probes for excitatory receptor in the brain that use glutamate as the neurotransmitter.